The integrins comprise a large family of heterodimeric transmembrane receptors that mediate both cell-cell and cell-matrix interactions. They engage numerous ligands and regulate a variety of cellular and physiological processes such as cell proliferation, apoptosis, migration, differentiation, inflammation and tissue remodelling. The α4β1 integrin is expressed mainly on leukocytes but is also found on smooth muscle cells and tumor cells. It has received particular attention because of its putative role in modulating the inflammatory response, promoting the exfiltration of leukocytes from the circulation. The α4β7 integrin is also thought to play a role in the inflammatory process.
Osteopontin (OPN) is an RGD containing extracellular matrix protein expressed by a number of cell types including osteoclasts, osteoblasts, macrophages, activated T-cells, smooth muscle cells and epithelial cells. It is present in several tissues including bone, kidney, placenta, smooth muscle and secretory epithelia and is associated with normal tissue remodelling processes such as bone resorption, angiogenesis, wound healing and tissue injury as well as certain diseases including restenosis, atherosclerosis, renal diseases and tumorigenesis. Upon infection and damage OPN expression is rapidly upregulated by T cells and macrophages. It acts as a chemoattractant for smooth muscle cells, and may facilitate further recruitment and activation of both T-cells and macrophages. In addition it may also act as a costimulatory molecule for T-cells. The diverse functions of osteopontin suggest that it may be important in both the immune-response and tissue remodelling.
OPN exerts many of its biological effects by interacting with integrins. It constutively binds αvβ3, αvβ5, αvβ1 and α8β1 via a central RGD motif, while proteolytic modification of OPN by thrombin cleavage at aa168 reveals cryptic binding sites for α9β1 and α5β1.